Lab Notes: Impulse May Be Hard-Wired

by MedPage Today Staff

A murine model may hold the key to unlocking the relationship between stress and PTSD, while that checkout "impulse buy" may be explained by genes rather than marketing, according to reports in this week's Lab Notes.

Impulse Shopper? We've Got a Gene for That

Genetic factors may be behind making brash decisions. A team of scientists from the National Institutes of Health found that among Finnish inmates, a mutation in the HTR2B gene predicted impulsive behavior. This gene encodes a specific brain receptor for serotonin, a neurotransmitter involved in decision making.

The researchers looked at a sample of violent criminal offenders in Finland, all of whom had committed spontaneous and purposeless crimes, and compared them with normal controls.

The scientists chose this population because Finns are descended from a relatively small number of original settlers, which has reduced the genetic complexity of diseases in that country. Thus, they increased their chances of finding genes that influence impulsive behavior.

They found that 7.46% of the violent offenders had the mutation, compared with 2.32% of controls.

Yet, the genetic variant alone wasn't enough to cause people to act rashly. HTR2B carriers who committed violent crimes were male and had only become violent when they were drunk -- a state that in itself leads to a lack of inhibition.

Aside from this limitation, the findings, published in Nature, are limited to Finns.

K.F.

Acetylcholine Boost May Reduce Fatigue

Boosting acetylcholine production might offer a novel strategy for treating neuromuscular disorders and other conditions associated with fatigue, according to a preclinical gene-therapy study.

Mice doubled their baseline endurance on a treadmill after insertion of a gene for choline transporter into the neuromuscular junction, investigators reported in Neuroscience.

"We reasoned that giving more of this protein might enhance muscle function and reduce nerve-dependent fatigue," Randy Blakely, PhD, of Vanderbilt University in Nashville, Tenn., said in a statement.

The strategy could help pave the way to a new therapeutic approach for a wide range of medical conditions associated with choline signaling deficits, including: myasthenia gravis, muscular dystrophy, congestive heart failure, depression, schizophrenia, Alzheimer's disease, and attention-deficit hyperactivity disorder (ADHD).

The investigators previously reported that a variant of the choline transport gene is associated with combined ADHD.

"The brain uses acetylcholine for a wide variety of functions, including the ability to sustain attention," Blakely said.

C.B.

What Rats Can Tell Us About PTSD

One characteristic of posttraumatic stress disorder (PTSD) and related disorders is the formation of negative associations with stimuli that are unrelated to the trauma. It is unknown, however, how stress contributes to that phenomenon.

To find out, researchers led by André Fenton, PhD, of New York University, conducted several experiments in rats. They first taught the animals how to navigate a T-shaped maze. The next day, they subjected some of the rats to stress by forcing them to swim in a bucket of water. The other rats were not stressed.

After that, the researchers put the rats in the maze again. The animals that were stressed had a better memory for which way to turn in the maze.

"Our results show that stress can activate memory, even if that memory is unrelated to the stressful experience," Fenton said in a statement.

He said further studies on the link between stress and memories may help in understanding PTSD and other anxiety and mood disorders.

In PLoS Medicine, Fenton's team wrote, "These findings that a stressful experience itself can activate memory suggest the novel hypothesis that traumatic stress reactivates pre-trauma memories, linking them to memory for the trauma and pathological facilitation of post-traumatic recall."

T.N.

Amyloid in CSF Predicts Brain Atrophy

Healthy adults willing to undergo a spinal tap can get a clue to their risk of future brain shrinkage, according to a British study published online in Annals of Neurology.

A low level of long-form beta-amyloid protein in cerebrospinal fluid was significantly associated with brain atrophy a year later, as measured by cranial MRI in 105 cognitively normal volunteers.

But one-quarter of participants with low CSF amyloid levels had no or minimal atrophy, whereas about one-third of those with high levels showed atrophy of at least 5 ml per year. Moreover, the study collected almost no data on clinical features -- despite headlines in British newspapers suggesting the CSF test could predict Alzheimer's disease.

J.G.

Liver's Fountain of Youth Found

A cellular pathway best known for being the target of cancer and anti-rejection drug rapamycin (Sirolimus) appears to control aging of the liver, researchers reported in Nature. Aging leads to decline in the liver's ability to produce ketones to provide energy for the heart and brain during sleep and other times of low carbohydrate intake.

Boosting activity of the mechanistic target of rapamycin complex 1 (mTORC1) pathway caused ketones to fall in young mice but levels remained at the same low levels in old mice, suggesting it was an aging-related switch that had already been shut off. Blocking mTORC1 in young mice prevented age-related decline in ketone production by the liver.

Suppressing this pathway with rapamycin could slow aging, but the researchers recommended against long-term use for this purpose, which would likely carry risks. Rather, figuring out why aging impacts ketones through mTORC1 may be the next step toward harnessing this fountain of youth for the liver.

C.P.

Algae Fights ALS

Dietary supplementation with the blue-green algae spirulina-used as a food by the Aztecs for thousands of years-could hold promise for patients with amyotrophic lateral sclerosis (ALS), an animal study suggested.

Researchers have suggested that oxidative damage may be involved in the inexorable neurodestruction of ALS, along with upregulation of pro-inflammatory cytokines. Spirulina contains phycocyanins, which have potent antioxidant and anti-inflammatory effects that could be neuroprotective.

To test this hypothesis, a group led by Svitlana Garbuzova-Davis, PhD, of the University of South Florida in Tampa compared the effects of dietary supplementation with 0.1% spirulina in a mouse model of ALS.

They found that mice fed the supplement maintained their weight and hindfoot extension reflexes after ten weeks of treatment significantly better than mice fed a control diet. The spirulina-fed mice also had less spinal cord neurodegeneration at 15 weeks.

"Our results showed that the spirulina dietary supplement slowed the onset of motor symptoms and disease progression, reducing inflammatory markers and motor neuron death in G93A mice," the researchers wrote in the Open Tissue Engineering and Regenerative Medicine Journal.

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